We propose to test a novel PET (Positron Emission Tomography) imaging-based method to select and optimize the delivery of systemic chemotherapy to patients suffering from metastatic non-small cell lung cancer, the leading cause of cancer death in the United States. We will build on the work of Weber and colleagues, which demonstrated that the change in the primary tumor FDG uptake by PET after a single cycle of platinum-based chemotherapy revealed which metastatic NSCLC (Non-Small Cell Lung Cancer) patients had longer progression-free and overall survival after administration of the entire multi-cycle chemotherapy regimen. We are proposing a clinical trial to test the hypothesis that, for a given patient, outcome from chemotherapy can be improved by determining early tumor response with FDG PET and changing chemotherapy agents in the event of poor response by PET. We will assess response rates in initially non- responding patients who would be expected to have an extremely low response rate if the initial chemotherapy were continued. The ability of FDG-PET to predict response to therapy as measured by CT will also be assessed. Finally, we will evaluate the early and late changes in tumor FDG uptake (Delta SUV) (Standardized Uptake Value) in all subjects and correlate it to their overall survival. This proposal serves to rapidly translate observational data on the predictive power of FDG-PET into an image guided intervention for chemotherapy selection. The data collected will help establish FDG-PET as a valuable tool for monitoring treatment response and for rapidly tailoring chemotherapy. [unreadable] [unreadable] FDG-PET based chemotherapy selection has the potential to improve outcomes for patients with metastatic NSCLC by optimizing the benefit of chemotherapy with tailored therapy. With over 70,000 patients diagnosed with metastatic non-small cell lung cancer each year in the US and a 2% 5-yr survival, even small gains in our ability to optimize therapy would translate into thousands of person-years saved. If validated, this technique could be extended to the neo-adjuvant setting, where improved therapy will result in higher cure rates for patients with operable lung cancer. FDG-PET based chemotherapy selection has the potential to improve outcomes for patients with metastatic NSCLC by optimizing the benefit of chemotherapy with tailored therapy. With over 70,000 patients diagnosed with metastatic non-small cell lung cancer each year in the US and a 2% 5-yr survival, even small gains in our ability to optimize therapy would translate into thousands of person-years saved. If validated, this technique could be extended to the neo-adjuvant setting, where improved therapy will result in higher cure rates for patients with operable lung cancer [unreadable] [unreadable] [unreadable]